RESUMEN
OBJECTIVE: To characterize severe potential drug interactions in maternal intensive care, and to determine their frequency, risk factors and potential risk medications. METHODS: An observational and longitudinal study conducted between December 2014 and December 2015 in a maternal intensive care unit. Clinical data were collected and severe potential drug interactions were identified on pregnant inpatients. The drug interactions were classified by type, prevalence and exposure rate. A multivariate logistic regression model was used to identify the severe potential drug interactions and the related drugs (p<0.05). RESULTS: A total of 95.1% of patients were exposed to, at least, one potential drug interaction; in that, 91.7% 33.9% were related to, respectively, moderate and severe potential drug interactions. The patients were exposed, on average, on 69.2% of days they were in the intensive care unit. The main drugs involved in more severe drug interactions were magnesium sulfate, metoclopramide, propranolol and diazepam. CONCLUSION: The severe potential drug interactions were observed in almost all patients of the study, and, approximately one third of those interactions were related to greater severity and resulted in exposure during long hospital stay. The higher number of prescribed drugs and its previous use of medications at home increase the occurrence of severe potential drug interactions.
Asunto(s)
Interacciones Farmacológicas , Unidades de Cuidados Intensivos/estadística & datos numéricos , Embarazo/efectos de los fármacos , Medición de Riesgo/métodos , Adolescente , Adulto , Brasil/epidemiología , Estudios Transversales , Diazepam/farmacología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Modelos Logísticos , Sulfato de Magnesio/farmacología , Metoclopramida/farmacología , Análisis Multivariante , Prevalencia , Propranolol/farmacología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
INTRODUCTION AND AIMS: Critically ill patients present with a broad spectrum of gastrointestinal motility disorders that affect the digestive tract. Our aim was to compare the effect of two prokinetic drugs on gastric electrical rhythm in critically ill septic patients, measured through surface electrogastrography (EGG). MATERIAL AND METHODS: A prospective triple-blinded randomized study was conducted on 36 patients admitted to the intensive care unit (ICU) with the diagnosis of septic shock. They were randomized to receive metoclopramide or domperidone. We assessed dominant frequency (DF), percentage distribution over time, and dominant power (DP), which represents the strength of contraction, before and after administration of the study drugs. RESULTS: Reliable electrogastrograms were achieved in all patients. In relation to the distribution of DF over time, 64% of patients had dysrhythmia, the mean baseline DF was 2.9 cpm, and the mean DP was 56.5µv After drug administration, 58% of the patients had dysrhythmia, the mean DF increased to 5.7 cpm (P<.05), and the DP did not change (57.4µv2). There were no significant differences between drugs. In the metoclopramide group, the baseline DF was 2.1 cpm and the baseline DP was 26.1µv2. The post-drug values increased to 5.4 cpm and 34.1µv2, respectively. In the domperidone group, the baseline DF was 3.7 cpm and the baseline DP was 86.9µv2. After drug administration, the DF increased to 6.1 cpm and the DP decreased to 83.5µv2. CONCLUSIONS: Both metoclopramide and domperidone similarly increased the DF of gastric pacemaker activity and improved gastric motility by restoring a normogastric pattern. Gastric dysmotility is frequent in septic patients.
Asunto(s)
Antieméticos/farmacología , Enfermedad Crítica , Domperidona/farmacología , Endoscopía Gastrointestinal/métodos , Motilidad Gastrointestinal , Metoclopramida/farmacología , Sepsis/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Electrodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios ProspectivosRESUMEN
ABSTRACT Objective: To characterize severe potential drug interactions in maternal intensive care, and to determine their frequency, risk factors and potential risk medications. Methods: An observational and longitudinal study conducted between December 2014 and December 2015 in a maternal intensive care unit. Clinical data were collected and severe potential drug interactions were identified on pregnant inpatients. The drug interactions were classified by type, prevalence and exposure rate. A multivariate logistic regression model was used to identify the severe potential drug interactions and the related drugs (p<0.05). Results: A total of 95.1% of patients were exposed to, at least, one potential drug interaction; in that, 91.7% 33.9% were related to, respectively, moderate and severe potential drug interactions. The patients were exposed, on average, on 69.2% of days they were in the intensive care unit. The main drugs involved in more severe drug interactions were magnesium sulfate, metoclopramide, propranolol and diazepam. Conclusion: The severe potential drug interactions were observed in almost all patients of the study, and, approximately one third of those interactions were related to greater severity and resulted in exposure during long hospital stay. The higher number of prescribed drugs and its previous use of medications at home increase the occurrence of severe potential drug interactions.
RESUMO Objetivo: Caracterizar as interações medicamentosas potenciais graves em terapia intensiva materna, e determinar sua frequência, os fatores e os medicamentos de risco associados à ocorrência dessas interações. Métodos: Estudo observacional e longitudinal executado entre dezembro de 2014 a dezembro de 2015, conduzido em uma unidade de terapia intensiva materna. Foram coletados dados clínicos e identificadas interações medicamentosas potenciais graves de gestantes admitidas. As interações medicamentosas foram caracterizadas quanto ao tipo, à prevalência e à taxa de exposição. Um modelo multivariado de regressão logística foi utilizado para identificação de fatores associados à ocorrência de interações medicamentosas potenciais graves e os medicamentos implicados (p<0,05). Resultados: Um total de 95,1% das pacientes foi exposto a, no mínimo, uma interação medicamentosa potencial, com 91,7% delas envolvidas com interações medicamentosas potenciais moderadas e 33,9% com as interações graves. As pacientes ficaram expostas, em média, em 69,2% dos dias que estiveram sob terapia intensiva. Os principais medicamentos implicados em interações medicamentosas de maior gravidade foram sulfato de magnésio, metoclopramida, propranolol e diazepam. Conclusão: As interações medicamentosas potenciais graves ocorreram na maioria das pacientes avaliadas. Aproximadamente um terço das interações foram graves e levaram à maior exposição por um longo período de internação. Maior número de fármacos prescritos e uso prévio domiciliar de medicamentos elevam a ocorrência de interações medicamentosas potenciais graves.
Asunto(s)
Humanos , Femenino , Niño , Adolescente , Adulto , Adulto Joven , Medición de Riesgo/métodos , Interacciones Farmacológicas , Unidades de Cuidados Intensivos/estadística & datos numéricos , Metoclopramida/farmacología , Propranolol/farmacología , Índice de Severidad de la Enfermedad , Brasil/epidemiología , Embarazo/efectos de los fármacos , Modelos Logísticos , Estudios Transversales Seriados , Prevalencia , Análisis Multivariante , Factores de Riesgo , Diazepam/farmacología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Hospitalización/estadística & datos numéricos , Sulfato de Magnesio/farmacologíaRESUMEN
A better understanding of the factors influencing the biology of amphibian spermatozoa after release from the testis is a prerequisite to the development of sperm preservation methods. The objective of the study was to determine the effect of extracellular conditions (exposure to water and different temperatures) over time on the sperm motility and structural properties (including morphology and DNA integrity) collected from hormonally stimulated Atelopus zeteki. Following intraperitoneal injection of gonadotropin-releasing hormone agonist (des-Gly10, D-Ala6, Pro-NHEt9 GnRH; 4 µg/g of body weight), human chorionic gonadotropin (hCG, 10 IU/gbw), or Amphiplex™ (0.4 µg/gbw GnRH-A + 10 µg/gbw metoclopramide hydrochloride), spermic urine samples from 27 males were collected and analyzed for sperm motility, morphology and DNA integrity while maintained at room temperature (23 °C), 4 °C, or diluted in water (hypo-osmotic environment) over a period of 46 min post-collection. Percentages of sperm motility and forward progressive motility remained high (>60%) when spermic urine was kept at room temperature or at 4 °C for 46 min regardless of the hormonal stimulation method. Dilution in water at room temperature greatly reduced the percentage of motile spermatozoa and forward progression (<50%) as well as DNA integrity (32.8% of intact cells) after 23 min while morphology did not differ (30.4% of normal cells), regardless of the hormone stimulation. This is the first systematic study on the effect of extracellular environment over time on A. zeteki sperm quality. This will contribute to the development of sperm handling protocols and reproductive technologies for this and other endangered Atelopus species.
Asunto(s)
Anuros/fisiología , Espermatozoides/fisiología , Animales , Gonadotropina Coriónica/farmacología , Daño del ADN , Especies en Peligro de Extinción , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/farmacología , Masculino , Metoclopramida/farmacología , Análisis de Semen/veterinaria , Motilidad Espermática/efectos de los fármacosRESUMEN
Case report of a 39-year-old intended mother of a surrogate pregnancy who underwent induction of lactation by sequential exposure to galactagogue drugs (metoclopramide and domperidone), nipple mechanical stimulation with an electric pump, and suction by the newborn. The study aimed to analyze the effect of each step of the protocol on serum prolactin levels, milk secretion and mother satisfaction, in the set of surrogacy. Serum prolactin levels and milk production had no significant changes. Nevertheless, the mother was able to breastfeed for four weeks, and expressed great satisfaction with the experience. As a conclusion, within the context of a surrogate pregnancy, breastfeeding seems to bring emotional benefits not necessarily related to an increase in milk production.
Asunto(s)
Lactancia Materna , Domperidona/farmacología , Lactancia/efectos de los fármacos , Metoclopramida/farmacología , Prolactina/sangre , Prolactina/efectos de los fármacos , Adulto , Femenino , Humanos , Satisfacción Personal , Madres SustitutasRESUMEN
Abstract Case report of a 39-year-old intended mother of a surrogate pregnancy who underwent induction of lactation by sequential exposure to galactagogue drugs (metoclopramide and domperidone), nipple mechanical stimulation with an electric pump, and suction by the newborn. The study aimed to analyze the effect of each step of the protocol on serum prolactin levels, milk secretion and mother satisfaction, in the set of surrogacy. Serum prolactin levels and milk production had no significant changes. Nevertheless, themother was able to breastfeed for four weeks, and expressed great satisfaction with the experience. As a conclusion, within the context of a surrogate pregnancy, breastfeeding seems to bring emotional benefits not necessarily related to an increase in milk production.
Resumo Relato de caso de mãe por útero de substituição, de 39 anos de idade, submetida a indução da lactação por exposição sequencial a drogas galactogogas (metoclopramida e domperidona), estimulação mamilar mecânica com bomba elétrica, e sucção pelo recém-nascido. O estudo teve como objetivo analisar os efeitos de cada etapa do protocolo na concentração sérica de prolactina, no volume de secreção láctea e na satisfação materna. A concentração sérica de prolactina e a produção láctea não apresentaram mudanças significativas. Entretanto, a mãe foi capaz de amamentar a criança por quatro semanas, e manifestou grande satisfação com a experiência. Como conclusão, no contexto de maternidade por útero de substituição, o aleitamento materno parece promover benefícios emocionais, não necessariamente relacionados ao aumento do volume de leite.
Asunto(s)
Humanos , Femenino , Adulto , Lactancia Materna , Domperidona/farmacología , Lactancia/efectos de los fármacos , Metoclopramida/farmacología , Prolactina/sangre , Prolactina/efectos de los fármacos , Satisfacción Personal , Madres SustitutasRESUMEN
The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the tibial epiphyseal plate of hormone-treated oophorectomized mice. For this purpose, 18 animals with intact ovaries were allocated to two groups, M (metoclopramide) and V (vehicle). One hundred and eight oophorectomized animals were allocated to 12 subgroups: Oophx/V (vehicle); Ooph/M (metoclopramide); Oophx/V + E (vehicle + estradiol); Oophx/M + E (metoclopramide + estradiol); Oophx/V + P (vehicle + progesterone); Oophx/M + P (metoclopramide + progesterone); Oophx/V + T (vehicle + testosterone); Oophx/M + T (metoclopramide + testosterone); Oophx/V + E + P (Vehicle + estradiol + progesterone); Oophx/M + E + P (metoclopramide + estradiol + progesterone); Oophx/V + E + P + T (vehicle + estradiol + progesterone + testosterone); Oophx/M + E + P + T (metoclopramide + estradiol + progesterone + testosterone). After a 50-day treatment was performed histomorphometric and immunohistochemical cell death analysis. In the epiphyseal plate of the hyperprolactinemic and/or oophorectomized animals, cell proliferation and bone formation decreased, inducing intensified cell death. In the sex steroid-treated animals, estrogen boosted cell proliferation; progesterone, bone formation and testosterone, both cell proliferation and bone formation. These findings suggest that oophorectomy and hyperprolactinemia changed epiphyseal plate morphology causing cartilage degeneration. Treatment with combined sex steroids may diminish such deleterious effects.
Asunto(s)
Andrógenos/farmacología , Estrógenos/farmacología , Placa de Crecimiento/efectos de los fármacos , Hiperprolactinemia , Metoclopramida/farmacología , Osteogénesis/efectos de los fármacos , Progestinas/farmacología , Tibia/efectos de los fármacos , Animales , Cartílago Articular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Antagonistas de los Receptores de Dopamina D2 , Estradiol/farmacología , Femenino , Ratones , Ovariectomía , Progesterona/farmacología , Testosterona/farmacologíaRESUMEN
This study aimed to establish a hormonal induction protocol for spermiation of Brycon cephalus males, using Ala6, Pro9Net-mGnRH + metoclopramide (Ovopel®). Thus, 20 males were used divided into three inductor treatments [â pellet/kg (T1), â pellet/kg (T2) and 1â pellet/kg (T3)] and one control group (CO), which only received physiological solution applications (0.9% NaCl). All treatments were applied in a single dose. For evaluation of the availability of the treatment, the following seminal parameters were analyzed: seminal volume, subjective spermatic motility, duration of motility, pH, osmolality and spermatic concentration. T3 showed the highest seminal volume (4.66 ± 1.52 ml), and was significantly different in comparison with T1 (2.0 ± 0.9 ml), T2 (3.5 ± 1.3 ml) and CO (2.3 ± 1.2 ml). In relation to spermatic motility, T2 and T3 showed significantly higher levels [5, (81-100%)]. However, T3 showed significantly lower average sperm motility duration than T1, T2 and CO (30 ± 7 s; 28 ± 6 s; 32 ± 8 s, respectively). With regard to the seminal parameters of spermatic concentration, pH and osmolality, no significant variation was verified among treatments. In conclusion, mGnRH + metoclopramide used for hormonal induction of B. cephalus reproduction does not induce changes related to spermatic concentration, pH and osmolality parameters of the seminal fluid and the most adequate doses among tested treatments were â pellet/kg live fish.
Asunto(s)
Characiformes/fisiología , Hormona Liberadora de Gonadotropina/farmacología , Metoclopramida/farmacología , Semen/efectos de los fármacos , Animales , Antagonistas de los Receptores de Dopamina D2/farmacología , Hormona Liberadora de Gonadotropina/análogos & derivados , Concentración de Iones de Hidrógeno , Masculino , Concentración Osmolar , Semen/citología , Semen/metabolismo , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Factores de TiempoRESUMEN
PURPOSE: To evaluate the effects of metoclopramide on metalloproteinases (MMP) and interleukins (IL) gene expression in colonic anastomoses in rats. METHODS: Eighty rats were divided into two groups for euthanasia on the 3rd or 7th postoperative day (POD), then into two subgroups for sepsis induction or not, and then into subgroups to receive either metoclopramide or saline solution. Left colonic anastomosis were performed and then analyzed. RESULTS: On the 3rd POD, metoclopramide was associated with increased expression of MMP-1a, MMP-13, and TNF-α. On the 7th POD, the transcripts of all MMPs, TNF-α, IL-1ß, IFN-γ, and IL-10 of the treated animals became negatively modulated. In the presence of sepsis, metoclopramide did not change MMPs and decreased IL-6, IL-1ß, IFN-γ and IL-10 gene expression on the 3rd POD. On the 7th POD, increased expression of all MMPs, IFN-γ and IL-10 and negative modulated TNF-α and IL-6 gene expression. CONCLUSION: Administration of metoclopramide increased metalloproteinases and interleukins gene expression on the 3rd postoperative day and negatively modulated them on the 7th POD. In the presence of abdominal sepsis, metoclopramide did not change MMPs and decreased ILs gene expression on the 3rd POD. On the 7th POD, the drug increased expression of all MMPs.
Asunto(s)
Antieméticos/farmacología , Colon/cirugía , Expresión Génica/efectos de los fármacos , Interleucinas/metabolismo , Metaloproteasas/efectos de los fármacos , Metoclopramida/farmacología , Anastomosis Quirúrgica , Animales , Modelos Animales de Enfermedad , Infecciones Intraabdominales/etiología , Masculino , Metaloproteasas/metabolismo , Periodo Posoperatorio , Distribución Aleatoria , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Sepsis/etiología , Cicatrización de Heridas/efectos de los fármacosRESUMEN
PURPOSE : To evaluate the effects of metoclopramide on metalloproteinases (MMP) and interleukins (IL) gene expression in colonic anastomoses in rats. METHODS : Eighty rats were divided into two groups for euthanasia on the 3rd or 7th postoperative day (POD), then into two subgroups for sepsis induction or not, and then into subgroups to receive either metoclopramide or saline solution. Left colonic anastomosis were performed and then analyzed. RESULTS : On the 3rd POD, metoclopramide was associated with increased expression of MMP-1a, MMP-13, and TNF-α. On the 7th POD, the transcripts of all MMPs, TNF-α, IL-1β, IFN-γ, and IL-10 of the treated animals became negatively modulated. In the presence of sepsis, metoclopramide did not change MMPs and decreased IL-6, IL-1β, IFN-γ and IL-10 gene expression on the 3rd POD. On the 7th POD, increased expression of all MMPs, IFN-γ and IL-10 and negative modulated TNF-α and IL-6 gene expression. CONCLUSION : Administration of metoclopramide increased metalloproteinases and interleukins gene expression on the 3rd postoperative day and negatively modulated them on the 7th POD. In the presence of abdominal sepsis, metoclopramide did not change MMPs and decreased ILs gene expression on the 3rd POD. On the 7th POD, the drug increased expression of all MMPs.
Asunto(s)
Animales , Masculino , Antieméticos/farmacología , Colon/cirugía , Expresión Génica/efectos de los fármacos , Interleucinas/metabolismo , Metaloproteasas/efectos de los fármacos , Metoclopramida/farmacología , Anastomosis Quirúrgica , Modelos Animales de Enfermedad , Infecciones Intraabdominales/etiología , Metaloproteasas/metabolismo , Periodo Posoperatorio , Distribución Aleatoria , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Sepsis/etiología , Cicatrización de Heridas/efectos de los fármacosRESUMEN
In fish, in vitro fertilization is an important reproductive tool used as first step for application of others biotechniques as chromosome and embryo manipulation. In this study, we aimed to optimize gamete quality and their short-term storage from the yellowtail tetra Astyanax altiparanae, for future application in laboratory studies. Working with sperm, we evaluated the effects of spawning inducers (carp pituitary gland and Ovopel® [(D-Ala6, Pro9-NEt) - mGnRH+metoclopramide]) and the presence of female on sperm motility. Additionally, we developed new procedures for short-term storage of sperm and oocytes. Briefly, sperm motility was higher when male fish were treated with carp pituitary gland (73.1 ± 4.0%) or Ovopel® (79.5 ± 5.5%) when compared with the control group treated with 0.9% NaCl (55.6 ± 27.2%; P=0.1598). Maintenance of male fish with an ovulating female fish also improved sperm motility (74.4 ± 7.4%) when compared with untreated male fish (42.1 ± 26.1%; P=0.0018). Storage of sperm was optimized in modified Ringer solution, in which the sperm was kept motile for 18 days at 2.5°C. The addition of antibiotics or oxygen decreased sperm motility, but partial change of supernatant and the combination of those conditions improve storage ability of sperm. Fertilization ability of oocytes decreased significantly after storage for 30, 60 90 and 120 min at 5, 10, 15 and 20°C when compared with fresh oocytes (P=0.0471), but considering only the stored samples, the optimum temperature was 15°C. Those data describe new approaches to improve semen quality and gametes short-term storage in yellowtail tetra A. altiparanae and open new possibilities in vitro fertilization.
Asunto(s)
Animales de Laboratorio/fisiología , Biotecnología/métodos , Characiformes/fisiología , Fertilización In Vitro/métodos , Espermatozoides/efectos de los fármacos , Análisis de Varianza , Animales , Femenino , Fertilización/fisiología , Hormona Liberadora de Gonadotropina/farmacología , Masculino , Metoclopramida/farmacología , Oocitos/efectos de los fármacos , Hipófisis/química , Preservación de Semen/métodos , Motilidad Espermática/efectos de los fármacos , Temperatura , Factores de TiempoRESUMEN
Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1α, MMP-8, MMP-13, IL-β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). On the third POD, bromopride was associated with increased MMP-1α, MMP-13, IL-6, IFN-γ, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-γ gene expression and decreased MMP-1, TNF-α, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-α. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process.
Asunto(s)
Animales , Masculino , Antieméticos/farmacología , Colon Descendente/cirugía , Expresión Génica/efectos de los fármacos , Interleucinas/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Metoclopramida/análogos & derivados , Anastomosis Quirúrgica , Ciego/cirugía , Interferón gamma/análisis , Interleucina-1beta/análisis , /análisis , /análisis , Interleucinas/genética , Ligadura , Metaloproteinasa 1 de la Matriz/análisis , /análisis , /análisis , Metaloproteinasas de la Matriz/genética , Metoclopramida/farmacología , Punciones , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sepsis/etiología , Factor de Necrosis Tumoral alfa/análisis , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1α, MMP-8, MMP-13, IL-ß, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). On the third POD, bromopride was associated with increased MMP-1α, MMP-13, IL-6, IFN-γ, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-γ gene expression and decreased MMP-1, TNF-α, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-α. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process.
Asunto(s)
Antieméticos/farmacología , Colon Descendente/cirugía , Expresión Génica/efectos de los fármacos , Interleucinas/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Metoclopramida/análogos & derivados , Anastomosis Quirúrgica , Animales , Ciego/cirugía , Interferón gamma/análisis , Interleucina-10/análisis , Interleucina-1beta/análisis , Interleucina-6/análisis , Interleucinas/genética , Ligadura , Masculino , Metaloproteinasa 1 de la Matriz/análisis , Metaloproteinasa 13 de la Matriz/análisis , Metaloproteinasa 8 de la Matriz/análisis , Metaloproteinasas de la Matriz/genética , Metoclopramida/farmacología , Punciones , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sepsis/etiología , Factor de Necrosis Tumoral alfa/análisis , Cicatrización de Heridas/efectos de los fármacosRESUMEN
UNLABELLED: In this work we have evaluated the gene expression profile of prolactin and prolactin receptor in the pituitary and the uterus of female mice with metoclopramide-induced hyperprolactinemia treated with estrogen and/or progesterone. For this purpose, 49 Swiss female mice were allocated to seven groups. INTERVENTIONS: 50-day treatment with metoclopramide, progesterone and estrogen. Our results showed that in the pituitary, metoclopramide-induced hyperprolactinemia increased prolactin expression. In the castrated animals, progesterone, with or without estrogen, produced an increase in prolactin. Pituitary prolactin receptor and the estrogen and progesterone treatment were responsible for the rise in PRLR-S2. In the uterus, no differences in prolactin expression were found between the different study groups. PRLR-S1 had its expression reduced in all castrated animals as against the castrated group treated with vehicle. In the noncastrated animals, PRLR-S2 rose in the metoclopramide-treated group, and, in the castrated animals, its expression diminished in all groups in relation to the vehicle-treated castrated controls. An increase in PRLR-S3 was found in the oophorectomized animals treated with a combination of estrogen and progesterone. PRLR-L rose in the oophorectomized animals treated with progesterone in isolation or in association with estrogen. These findings suggest that metoclopramide associated to progesterone or estrogen may determine an increase in pituitary prolactin and PRLR-S2 expression. The estrogen-progesterone may enhance the expression of PRLR-S3 and PRLR-L isoform of prolactin receptor.
Asunto(s)
Hiperprolactinemia/inducido químicamente , Metoclopramida/farmacología , Hipófisis/metabolismo , Receptores de Prolactina/metabolismo , Útero/metabolismo , Animales , Estrógenos/farmacología , Femenino , Ratones , Hipófisis/efectos de los fármacos , Progesterona/farmacología , Útero/efectos de los fármacosRESUMEN
INTRODUCTION: Metoclopramide is often used in the treatment of postoperative nausea and vomiting, but a literature review failed to find reports on the influence of this drug on the healing of bowel anastomoses in the setting of abdominal sepsis. The aim of this study was to evaluate the effects of metoclopramide on the healing of left colonic anastomoses in rats with induced abdominal sepsis. MATERIALS AND METHODS: Forty rats were divided into two groups of 20 animals each to receive either metoclopramide (experimental group: E) or saline (control group: C). Each group was further divided into subgroups of 10 animals each to be killed on the third (E3 and C3) or seventh postoperative day (E7 and C7). A segmental resection of the left colon was performed, followed by end-to-end anastomosis. Sepsis was induced by cecal ligation and puncture. On the day of reoperation, the total number of adhesions was assessed and the anastomosed bowel segment was removed for tensile strength testing, histopathological analysis, measurement of hydroxyproline levels, and histomorphometric evaluation of collagen. RESULTS: Intraoperative findings, number of intra-abdominal adhesions in the anastomosed area, and tensile strength before anastomosis rupture were similar among all subgroups at all assessments. On the third postoperative day, the anastomoses of animals treated with metoclopramide showed significantly lower hydroxyproline levels (p = 0.01) when compared with controls. Collagen content was similar among all subgroups. CONCLUSIONS: Metoclopramide does not have deleterious effects on the healing of bowel anastomoses in rats subjected to experimental abdominal sepsis.
Asunto(s)
Pared Abdominal/cirugía , Anastomosis Quirúrgica , Colon/cirugía , Metoclopramida/farmacología , Sepsis/cirugía , Cicatrización de Heridas/efectos de los fármacos , Animales , Ciego/cirugía , Modelos Animales de Enfermedad , Hidroxiprolina/metabolismo , Ligadura , Masculino , Punciones , Ratas , Ratas Wistar , Resistencia a la Tracción , Adherencias TisularesRESUMEN
PURPOSE: To assess the effect of prokinetic agents on abdominal wall wound healing in rats submitted to segmental colectomy and colonic anastomosis. METHODS: Sixty rats were randomly allocated into three groups according to the agents they would receive in the postoperative period: M (metoclopramide); B (bromopride); and C (control, saline 0.9%). Surgical procedures were performed identically in all animals, and consisted of a midline laparotomy followed by resection of a 1-cm segment of large bowel with end-to-end anastomosis. The abdominal wall was closed in two layers with running stitches. Abdominal wall samples were collected on the 3rd or 7th postoperative day for measurement of breaking (tensile) strength and histopathological assessment. RESULTS: There were no statistically significant differences in tensile strength of the abdominal wall scar between groups M, B, and C, nor between the three and seven days after surgery subgroups. On histopathological assessment, there were no statistically significant between-group differences in collagen deposition or number of fibroblasts at the wound site CONCLUSION: Use of the prokinetic drugs metoclopramide or bromopride had no effect on abdominal wall healing in rats submitted to segmental colectomy and colonic anastomosis.
Asunto(s)
Pared Abdominal , Colectomía , Colon/cirugía , Fármacos Gastrointestinales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Pared Abdominal/cirugía , Anastomosis Quirúrgica , Animales , Cicatriz/fisiopatología , Antagonistas de Dopamina/farmacología , Fármacos Gastrointestinales/uso terapéutico , Masculino , Metoclopramida/análogos & derivados , Metoclopramida/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Resistencia a la Tracción , Resultado del Tratamiento , Cicatrización de Heridas/fisiologíaRESUMEN
PURPOSE: To assess the effect of prokinetic agents on abdominal wall wound healing in rats submitted to segmental colectomy and colonic anastomosis. METHODS: Sixty rats were randomly allocated into three groups according to the agents they would receive in the postoperative period: M (metoclopramide); B (bromopride); and C (control, saline 0.9%). Surgical procedures were performed identically in all animals, and consisted of a midline laparotomy followed by resection of a 1-cm segment of large bowel with end-to-end anastomosis. The abdominal wall was closed in two layers with running stitches. Abdominal wall samples were collected on the 3rd or 7th postoperative day for measurement of breaking (tensile) strength and histopathological assessment. RESULTS: There were no statistically significant differences in tensile strength of the abdominal wall scar between groups M, B, and C, nor between the three and seven days after surgery subgroups. On histopathological assessment, there were no statistically significant between-group differences in collagen deposition or number of fibroblasts at the wound site CONCLUSION: Use of the prokinetic drugs metoclopramide or bromopride had no effect on abdominal wall healing in rats submitted to segmental colectomy and colonic anastomosis.
OBJETIVO: Avaliar os efeitos do uso de drogas prócinéticas na cicatrização da parede abdominal de ratos submetidos à colectomia segmentar e anastomose no cólon esquerdo. MÉTODOS: Foram utilizados 60 ratos, alocados aleatoriamente em três grupos para receberem as seguintes medicações no período pós-operatório: M (metoclopramida); B (bromoprida) e C (solução salina a 0,9%). Os procedimentos cirúrgicos foram idênticos em todos os animais. Foi realizada laparotomia mediana, seguida de colectomia segmentar de 1-cm e anastomose colônica. O fechamento da parede abdominal foi feito em dois planos de sutura contínua. No 3° ou no 7° dia pós-operatório foram coletadas amostras da parede abdominal para medida da força de ruptura e avaliação histopatológica. RESULTADOS: Não houve diferença significativa entre os grupos no que diz respeito à força de ruptura da parede abdominal, nem entre os subgrupos no 3º e 7º dia após a cirurgia. À análise histopatológica não houve alterações na deposição de colágeno ou na quantidade de fibroblastos no sítio da cicatriz. CONCLUSÃO: O uso de drogas prócinéticas, metoclopramida ou de bromoprida, não interferiu na cicatrização da parede abdominal de ratos submetidos à colectomia segmentar e anastomose no cólon esquerdo.
Asunto(s)
Animales , Masculino , Ratas , Pared Abdominal , Colectomía , Colon/cirugía , Fármacos Gastrointestinales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Pared Abdominal/cirugía , Cicatriz/fisiopatología , Antagonistas de Dopamina/farmacología , Fármacos Gastrointestinales/uso terapéutico , Metoclopramida/análogos & derivados , Metoclopramida/farmacología , Distribución Aleatoria , Ratas Wistar , Resistencia a la Tracción , Resultado del Tratamiento , Cicatrización de Heridas/fisiologíaRESUMEN
PURPOSE: To evaluate the effects of bromopride on the healing of left colonic anastomoses in rats with induced abdominal sepsis. METHODS: Forty rats were divided into two groups to receive either bromopride (experimental group- E) or saline (control group- C). Each group was divided into subgroups of ten animals each to be euthanized on third (E3 and C3) or seventh day (E7 and C7) after surgery. Sepsis was induced by cecal ligation and puncture. The rats underwent segmental left colon resection and end-to-end anastomosis. Adhesion formation, tensile strength and hydroxyproline concentration were assessed. Histomorphometry of collagen and histopathological analysis were also performed. RESULTS: On postoperative third day, anastomoses in bromopride-treated animals showed lower tensile strength (p=0.02) and greater reduction in hydroxyproline concentration (p=0.04) than in control animals. There was no statistical difference in these parameters on seventh day, and the remaining parameters were similar across subgroups. Collagen content was also similar across subgroups. CONCLUSION: In the presence of abdominal sepsis, the administration of bromopride was associated with decreased tensile strength and hydroxyproline concentration in left colonic anastomoses in rats three days after surgery.
Asunto(s)
Antieméticos/farmacología , Colon/cirugía , Metoclopramida/análogos & derivados , Sepsis/fisiopatología , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Animales , Colágeno/análisis , Colon/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Hidroxiprolina/análisis , Ligadura , Masculino , Metoclopramida/farmacología , Periodo Posoperatorio , Punciones , Ratas , Ratas Wistar , Sepsis/etiología , Resistencia a la TracciónRESUMEN
PURPOSE: To evaluate the effects of bromopride on the healing of left colonic anastomoses in rats with induced abdominal sepsis. METHODS: Forty rats were divided into two groups to receive either bromopride (experimental group- E) or saline (control group- C). Each group was divided into subgroups of ten animals each to be euthanized on third (E3 and C3) or seventh day (E7 and C7) after surgery. Sepsis was induced by cecal ligation and puncture. The rats underwent segmental left colon resection and end-to-end anastomosis. Adhesion formation, tensile strength and hydroxyproline concentration were assessed. Histomorphometry of collagen and histopathological analysis were also performed. RESULTS: On postoperative third day, anastomoses in bromopride-treated animals showed lower tensile strength (p=0.02) and greater reduction in hydroxyproline concentration (p=0.04) than in control animals. There was no statistical difference in these parameters on seventh day, and the remaining parameters were similar across subgroups. Collagen content was also similar across subgroups. CONCLUSION: In the presence of abdominal sepsis, the administration of bromopride was associated with decreased tensile strength and hydroxyproline concentration in left colonic anastomoses in rats three days after surgery.
OBJETIVO: Avaliar os efeitos da bromoprida sobre a cicatrização de anastomoses de cólon esquerdo de ratos na presença de sepse abdominal. MÉTODOS: Quarenta ratos distribuídos em grupos contendo 20 animais para administração de bromoprida ou salina. Cada grupo foi dividido em subgrupos contendo dez animais, para eutanásia no terceiro ou no sétimo dia de pós-operatório. A indução da sepse foi realizada pelo método de ligadura e punção do ceco. Foi realizada ressecção de um segmento do cólon esquerdo e anastomose término-terminal. À re-laparotomia, foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, força de ruptura, concentração de hidroxiprolina e histomorfometria do colágeno. RESULTADOS: No 3° DPO, as anastomoses dos animais tratados com bromoprida apresentaram menor força de ruptura (p=0,02) e maior redução da concentração de hidroxiprolina (p=0,04) que os animais controle. Não houve diferença estatística quanto a estes parâmetros no 7° DPO. O conteúdo de colágeno foi semelhante entre os subgrupos. CONCLUSÃO: Na presença de sepse abdominal, o uso da bromoprida esteve associado à diminuição da força de ruptura e da concentração de hidroxiprolina das anastomoses do cólon esquerdo de ratos no 3° DPO.
Asunto(s)
Animales , Masculino , Ratas , Antieméticos/farmacología , Colon/cirugía , Metoclopramida/análogos & derivados , Sepsis/fisiopatología , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Colágeno/análisis , Colon/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Hidroxiprolina/análisis , Ligadura , Metoclopramida/farmacología , Periodo Posoperatorio , Punciones , Ratas Wistar , Sepsis/etiología , Resistencia a la TracciónRESUMEN
This research aimed to evaluate the effect of metoclopramide and ranitidine in the prevention of gastroesophageal reflux episodes during anesthetic procedures. Ninety healthy female dogs were submitted to elective ovariosalpingohisterectomy, randomly divided into three groups of 30 animals. The control group received only the anesthetic protocol. The metoclopramide group received an intravenous bolus of 1mg/kg, and continuous infusion (1 mg/kg/h intravenously) immediately after anesthetic induction. The ranitidine group received an intravenous bolus of 2 mg/kg, 6 h before anesthesia. Anesthesia (acepromazine, propofol and isofluorane) was standardized and the esophageal pH variations were recorded. Esophagoscopy was carried out after surgery. No difference (p<0.05) was verified in the reflux episodes between the groups. Seven animals presented reflux. Metoclopramide in bolus and continuous infusion, as well as ranitidine, 6 h before anesthesia, did not influence the reduction of the incidence of gastroesophageal reflux.